MicroRNA-21 promotes cell proliferation, migration, and resistance to apoptosis through PTEN/PI3K/AKT signaling pathway in esophageal cancer

Wu, Yanran; Qi, Haijun; Deng, Danfang; Luo, Yingying; Yang, Shan

doi:10.1007/s13277-016-5074-2

Cited by 105 publications

(77 citation statements)

References 27 publications

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“…PTEN is associated with the occurrence of several types of tumor, and serves an important role in tumor cell growth, apoptosis, adhesion, migration and invasion (5). Previous studies have revealed that the downregulation or deletion of PTEN activates the phosphoinositide 3-kinase/RAC-α serine/threonine-protein kinase (PI3K/AKT) signaling pathway, resulting in the occurrence, development, invasion and metastasis of cancer (6,7).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of miRNA‑21 attenuates the proliferation and metastasis of human osteosarcoma by upregulating PTEN

Miu

et al. 2017

Exp Ther Med

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Abstract. The present study aimed to investigate the expression of micro (mi)RNA-21 in osteosarcoma cells, and its role in inhibiting the invasion and metastasis of osteosarcoma. Human osteosarcoma MG-63 cells and osteoblast hFOB1.19 cells were used to compare the expression of miRNA-21 using reverse transcription-quantitative polymerase chain reaction analysis. A miRNA-21 mimic or inhibitor were transfected into the MG-63 cells to upregulate and downregulate the expression of miRNA-21, respectively. The present study investigated the proliferation and invasion of transfected MG-63 cells using MTT and Transwell assays. Western blot analyses were used to investigate the regulation of important proteins in the phosphatase and tensin homolog/phosphoinositide 3-kinase/RAC-α serine/threonine-protein kinase (PTEN/PI3K/AKT) signaling pathway. Compared with hFOB1.19 cells, miRNA-21 expression was significantly upregulated in the MG-63 cells (P<0.01), which lead to increased proliferation. Downregulating miRNA-21 expression reduced the proliferation of MG-63 cells compared with hFOB1.19 cells. Invasion assays and western blot analyses revealed that the overexpression of miRNA-21 significantly enhanced the invasion ability of MG-63 cells and the expression of phosphorylated (p-)AKT, while downregulation of miRNA-21 expression reduced the protein level of AKT and p-AKT. In the MG-63 cells, miRNA-21 upregulation significantly inhibited the protein level of PTEN, resulting in significantly increased AKT and PI3K protein levels (P<0.01). In conclusion, the results of the present study indicate that the expression of miRNA-21, PI3K and AKT is increased in the osteosarcoma cell line MG-63, which results in reduced expression of PTEN and increased expression of proteins in the PI3K/AKT signaling pathway, and thus increases the aggressiveness of osteosarcoma cells.

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Section: Introductionmentioning

confidence: 99%

Inhibition of miRNA‑21 attenuates the proliferation and metastasis of human osteosarcoma by upregulating PTEN

Miu

et al. 2017

Exp Ther Med

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“…The tumor-suppressor PTEN is a well-known target of the miR-21-5p[43], and thus we aimed at addressing whether modulation of PTEN may influence our conclusion in this experimental system. First, we found that metformin treatment reduced colony formation and migration of the PTEN-devoid BT-549 cells (Figure 5a and b, respectively).…”

Section: Resultsmentioning

confidence: 99%

Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities

Pulito¹,

Mori²,

Sacconi³

et al. 2017

Cell Discov

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Metformin is a commonly prescribed type II diabetes medication that exhibits promising anticancer effects. Recently, these effects were found to be associated, at least in part, with a modulation of microRNA expression. However, the mechanisms by which single modulated microRNAs mediate the anticancer effects of metformin are not entirely clear and knowledge of such a process could be vital to maximize the potential therapeutic benefits of this safe and well-tolerated therapy. Our analysis here revealed that the expression of miR-21-5p was downregulated in multiple breast cancer cell lines treated with pharmacologically relevant doses of metformin. Interestingly, the inhibition of miR-21-5p following metformin treatment was also observed in mouse breast cancer xenografts and in sera from 96 breast cancer patients. This modulation occurred at the levels of both pri-miR-21 and pre-miR-21, suggesting transcriptional modulation. Antagomir-mediated ablation of miR-21-5p phenocopied the effects of metformin on both the clonogenicity and migration of the treated cells, while ectopic expression of miR-21-5p had the opposite effect. Mechanistically, this reduction in miR-21-5p enhanced the expression of critical upstream activators of the AMP-activated protein kinase, calcium-binding protein 39-like and Sestrin-1, leading to AMP-activated protein kinase activation and inhibition of mammalian target of rapamycin signaling. Importantly, these effects of metformin were synergistic with those of everolimus, a clinically relevant mammalian target of rapamycin inhibitor, and were independent of the phosphatase and tensin homolog status. This highlights the potential relevance of metformin in combinatorial settings for the treatment of breast cancer.

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“…PTEN gene mutation or deficiency and abnormal protein expression can promote cell proliferation and inhibit cell apoptosis, the expression of PTEN in malignant tumors is negatively correlated with tumor TNM staging, and meantime, the low expression of PTEN is closely related to chemotherapy resistance of breast cancer (Song et al, 2016); (Wu et al, 2016). In this study, the author has observed that the expression of PTEN in cells can be induced by silencing the expression of CD164 in U87 cells, so it is suspected that the apoptosis of glioma cells induced by CD164shRNA may be related to PTEN pathway.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2018

IRJMBS

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To investigate CD164 induced the apoptosis of U87 cell by down-regulating PTEN/PI3K/AKT signal pathway in vitro. Human CD164 sequence was used for the design of shRNA targeting CD164, which was then introduced to lentivirus, followed by transfection into U87 cells. The CCK-8 was used to investigate whether silencing of CD164 exert anti-proliferative and proapoptotic effects on U87 cells. Western blot assay was used to detect the expression of PTEN, p-AKT and p53 in U87 cells. After transfection with CD164 shRNA in U87 cells, human glioma cell line U87 with down-regulation of CD164 showed significant inhibition of cell proliferation compared with shRNA NC (P<0.001). Furthermore, CCK 8 result showed that apoptosis rate induced by the CD164 shRNA transfection was markedly higher than that of control (P<0.001). The western blot result demonstrated that the silencing of CD164 increased the levels of PTEN and p53, whereas the level of p-AKT was decreased by transduction of CD164 shRNA. CD164 may induce the apoptosis of U87 cell by down-regulating PTEN/PI3K/AKT signal pathway in vitro, providing a novel ideal to improving the diagnosis and treatment of glioma patients.

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MicroRNA-21 promotes cell proliferation, migration, and resistance to apoptosis through PTEN/PI3K/AKT signaling pathway in esophageal cancer

Cited by 105 publications

References 27 publications

Inhibition of miRNA‑21 attenuates the proliferation and metastasis of human osteosarcoma by upregulating PTEN

Inhibition of miRNA‑21 attenuates the proliferation and metastasis of human osteosarcoma by upregulating PTEN

Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities

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